Zuranolone
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Neuroactive steroid, GABA-A positive allosteric modulator (oral)
Zuranolone
Zurzuvae
Zuranolone (brand name Zurzuvae) is the first oral neuroactive steroid approved for postpartum depression, FDA-approved in August 2023. Like brexanolone, it acts as a positive allosteric modulator at GABA-A receptors, including extrasynaptic δ-containing subtypes thought to mediate antidepressant effect. Administered as a 14-day fixed-duration course rather than chronic daily dosing, an unusual paradigm in psychiatry. Initially studied for major depressive disorder (MDD) as well but the MDD application was rejected by FDA; only PPD problem approved.
Positive allosteric modulator at synaptic and extrasynaptic GABA-A receptors at the neuroactive steroid binding site, with affinity for δ-containing extrasynaptic receptors. Oral bioavailability with food enables outpatient dosing, unlike brexanolone's IV infusion.
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Effects
Somnolence (most common, can affect driving, black-box warning about CNS depressant activities for ≥12 hours after dose), dizziness, sedation, headache, diarrhea, fatigue. Suicidal thoughts reported.
Pharmacodynamics
Interactions
Fluoxetine via Category:Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
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Summary
Classes
Neuroactive steroid, GABA-A positive allosteric modulator (oral)
Common uses
Postpartum depression (PPD) in adults (FDA-approved 2023)
Pharmacy
Starting dose
50 mg PO once daily with fatty food in the evening × 14 days
Preparations
20 mg, 25 mg, 30 mg capsules
US FDA Max
50 mg/d × 14 d
Pharmacology
Routes
Oral
Onset
Day 3 of dosing in trials; sustained through day 45
Duration
14-day course; effect persists after discontinuation in trials
Half-life
~16-23 hours
Bioavailability
Adequate (food-dependent, must take with fatty meal)
Pregnancy
Limited data; avoid in pregnancy. Lactation: present in milk; consider risks
Legal status
Rx, Schedule IV (US)
Purported mechanism
Synthetic neuroactive steroid (an analog of allopregnanolone), bioavailable orally unlike brexanolone. Positive allosteric modulator at GABA-A receptors including extrasynaptic δ-containing subtypes.